Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes.

Bart Groen,Thera P Links,Marijke M Faas,Joop D Lefrandt,Paul De Vos,Gerrit Van Den Berg Gerrit Van Den Berg,Anne-Eva Van Der Wijk,Paul P Van Den Berg,Krystina M Sollie

doi:10.1038/srep13618

Bart Groen, Thera P Links + Show 7 more

Open Access

https://doi.org/10.1038/srep13618

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Abstract

Despite adequate glycemic control, pregnancy outcome of women with type 1 diabetes (T1D) is still unfavorable as compared to healthy women. In a rat-model of T1D under normoglycemic conditions, adverse pregnancy outcome was also observed, which was associated with aberrant immunological adaptations to pregnancy. Because similar processes may occur in women with T1D we studied the systemic immune response in non-pregnant and pregnant women with and without T1D. The systemic immune response was assessed by using flow cytometry to evaluate the number and activational status of subpopulations of lymphocytes, Natural Killer cells and monocytes in peripheral blood of non-pregnant and pregnant women with and without T1D. An increased white blood cell count, an increased Th1/Th2 ratio, increased Natural Killer cell expression of CD335 and enhanced activation of intermediate and non-classical monocytes was observed in pregnant women with T1D vs. healthy pregnant women. Also, the pregnancy outcome (i.e. incidence of preterm delivery and macrosomia) of women with T1D was unfavorable as compared to healthy women. This study showed that in T1D, the immunological adaptations to pregnancy are disturbed. In addition to hyperglycemia, these different immunological adaptations may be responsible for the greater frequency of complications in pregnant women with T1D.

Highlights

Normal pregnancy is accompanied by various immunological adaptations facilitating implantation, placentation and tolerance of the semi-allogeneic fetus[4,5,6]; aberrations in these adaptations are associated with pregnancy complications, like miscarriages, preeclampsia and preterm delivery[7,8,9]
Non-pregnant and pregnant women with type 1 diabetes (T1D) were recruited from the diabetes outpatient clinics of the University Medical Center Groningen (UMCG) and the Martini Hospital Groningen
Mean HbA1c was decreased in pregnant women with T1D as compared to non-pregnant women with T1D

Summary

Introduction

Normal pregnancy is accompanied by various immunological adaptations facilitating implantation, placentation and tolerance of the semi-allogeneic fetus[4,5,6]; aberrations in these adaptations are associated with pregnancy complications, like miscarriages, preeclampsia and preterm delivery[7,8,9]. Transitional state between classical and non-classical monocytes, of which the function is not exactly known yet[15] Their numbers are increased in pro-inflammatory conditions, such as preeclampsia and other inflammatory diseases[15,16]. The immune response in T1D patients is characterized by a type 1 immune response[17], impaired function of regulatory T-lymphocytes[18] and increased mRNA expression of interferon-gamma (IFN-γ )[19], when compared to healthy individuals. In view of this different immune response in T1D women, we hypothesized that pregnancy-induced immune adaptations differ between T1D and healthy pregnant women. Understanding these aberrant changes may be a first step toward designing new means, in addition to glycemic control, for preventing pregnancy complications in T1D pregnant women

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